Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults

Abstract

Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife.

Keywords: Alzheimer’s; arterial spin labeling; cerebral blood flow; cerebrovascular disease; diabetes.

Figures

Figure 1.

Relationship between Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (log 10) and arterial blood flow (mL/min) through the right (a) and left (b) internal carotid arteries, as assessed by phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR).

Figure 2.

Regions that showed a significant main effect of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on pseudo-continuous arterial spin labeling (pcASL) perfusion. Higher HOMA-IR was associated with lower cerebral perfusion in the, (a) right medial frontal gyrus and anterior cingulate, (b) left middle frontal gyrus, (c) right precentral gyrus, and the (d) right temporal lobe. This relationship is illustrated by the plot of HOMA-IR (log 10) and pcASL values extracted from the right temporal lobe gyrus (e). Clusters are significant at p = 0.001 (uncorrected) with a voxel extent threshold of > 50.

Figure 3.

Significant interaction of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and mean blood flow through bilateral internal carotid arteries (ICAs) on pseudo-continuous arterial spin labeling (pcASL) perfusion. A significant cluster was observed in the right superior frontal gyrus (a) where higher mean blood flow was associated with greater perfusion in individuals with lower but not higher HOMA-IR (b). Clusters are significant at p = 0.001 (uncorrected) with a voxel extent threshold of > 50. HOMA-IR is presented here as a median split for graphing purposes only.

Figure 4.

Relationship between Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and arterial blood flow (phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR)) in control (a) and metabolic syndrome (MetSyn) (b) groups.